反应详情

A mixture of potassium carbonate (95.3 g) and de-mineralized water (100 ml) was stirred for 10 to 15 minutes to dissolve the solid. The temperature of the mixture was maintained at 25° to 30° C. and dichloromethane (300 ml) was added to the mixture. (S)—N-[(2′-Cyanobiphenyl-4-yl)methyl]-(L)-valine benzyl ester hydrochloride (100 g) and tetrabutyl ammonium bromide (10.0 g) were added to the mixture. The reaction mixture was cooled to −10° to −8° C. and valeryl chloride (36.1 g) was added at −10° to −5° C. The reaction mixture was stirred for 60 to 90 minutes at 0° to 5° C. After the completion of the reaction, the temperature was raised to 25° to 30° C. De-mineralized water (200 ml) was added to the reaction mixture and the mixture was stirred for 1 hour at 25° to 30° C. The two phases were separated and the organic layer was washed with de-mineralized water (200 ml). The organic layer was concentrated at 40° to 45° C. to obtain a residual liquid containing the title compound.

1. dissolutionto dissolve the solid
2. temperatureThe temperature of the mixture was maintained at 25° to 30° C.
3. temperatureThe reaction mixture was cooled to −10° to −8° C.
4. stirringThe reaction mixture was stirred for 60 to 90 minutes at 0° to 5° C
5. customAfter the completion of the reaction
6. temperaturethe temperature was raised to 25° to 30° C
7. stirringthe mixture was stirred for 1 hour at 25° to 30° C
8. customThe two phases were separated
9. washthe organic layer was washed with de-mineralized water (200 ml)
10. concentrationThe organic layer was concentrated at 40° to 45° C.
11. customto obtain a residual liquid